AAOS Exclusive: Xiaflex Injections at the Forefront for Dupuytren’s Treatment

Dupuytren’s disease, or Dupuytren’s contracture, is a condition where the fingers bend towards the palm of the hand and cannot be straightened. The cause is small benign tumors in the soft tissue of the hand—palmar fibromatosis—causing the collagen type I in the region to become collagen type III which is significantly thicker. The disease is named for Baron Guillaume Dupuytren, a surgeon who described an operation to correction the affliction in an 1831 issue of the still-operational medical journal Lancet.

As explained by hand surgeon Craig S. Williams, M.D., at the 2014 Annual Meeting of the American Academy of Orthopaedic Surgeons, the disease primarily affects Caucasian males of northern European descent above the age of 40. The disease was first described on record in 1614, but evidence suggests the disease may trace all the way back to the Vikings.

“Treatment for Dupuytren’s is not benign,” Williams explained, “and there is no cure. We have to look at this as a ‘management’ situation. The most important thing we have to do as surgeons after diagnosis is educate the patient.”

Treatment options for Dupuytren’s currently include radiation treatment, and surgical intervention “has been a mainstay for 200 or so years,” according to Williams.

“The most extensive research into treatment is found in German medical literature,” Williams said. “There are some promising but really uncertain results in the literature suggesting that the early stages of Dupuytren’s, low dose radiation may prevent progression of the disease. However, concerns regarding long term effects of radiation make that not very popular in the United States.”

Despite the very long history of documentation on Dupuytren’s, it is only now that a technology has been developed for the treatment of the disease specifically. Collagenase clostridium histolyticum (CCH) is a secretion of the bacterium clostridium histolyticum, and can destroy connective tissues such as collagen. Auxilium Pharmaceuticals Inc., based in Chesterbrook, Pa., received U.S. Food and Drug Administration (FDA) approval for Xiaflex in 2010, an injectable combination of two collagenase enzymes derived from clostridium histolyticum. Xiaflex is meant to be injected—carefully, Williams warns, because of risk of tissue rupture—into the cords of collagen that have formed in the hand. Sometimes two or three injections are necessary, but the FDA only allows the injections to be 30 or more days apart. Some small scale studies have looked at injections administered in the same day, but they do not produce better results and only serve to increase the severity of a flare reaction, i.e. excessive swelling, pain and stiffness.

Injectable therapies are preferable to surgical interventions, said Williams.

“With surgery, digital nerve damage and wound healing is a problem,” he said. “A patient could get reflex sympathetic dystrophy syndrome. Maybe before, they could grasp a golf club, and now they can’t.”

Xiaflex is the result of decades of research.

“This is kind of a great story as it’s someone’s life work,” Williams said. “It tells a story over long period of time, showing how long it takes for an idea to come to fruition.”

The story begins in 1982 with Martin Gelbard, M.D., who led and published a study on the effects of CCH on elastic and collagen fibers in the corpora cavernosa (inside the penis), which is the secondary area this collagen build up can occur. Based on this groundwork, several more studies were conducted leading up to the randomized double blind study with a placebo in 2002, the phase three randomized double blind study in 2007, and the large-scale prospective multi center randomized trial that studied 308 Dupuytren’s patients in 2009. “Injectable Collagenase Clostridium Histolyticum for Dupuytren’s Contracture” was published in the New England Journal of Medicine, and demonstrated the efficacy of CCH over placebo with an overall success rate of 64 percent. A parallel study was run in Australia with similar but slightly less successful results. Finally, last year’s CORDLESS study looked at three-year follow up results from those patients.

When asked what other treatments and technologies could be on the horizon for the still incurable Dupuytren’s disease, Williams told Orthopedic Design & Technology that Xiaflex injections are currently at the forefront of the field.